Polyamines: pleiotropic molecules regulating plant development and enhancing crop yield and quality.

Polyamines (PAs) are pleiotropic bioorganic molecules. Cellular PA contents are determined by a balance between PA synthesis and degradation. PAs have been extensively demonstrated to play vital roles in the modulation of plant developmental processes and adaptation to various environmental stresses. In this review, the latest advances on the diverse roles of PAs in a range of developmental processes, such as morphogenesis, organogenesis, growth and development, and fruit ripening, are summarized and discussed. Besides, the crosstalk between PAs and phytohormones or other signalling molecules, including H2O2 and NO, involved in these processes is dwelled on. In addition, the attempts made to improve the yield and quality of grain and vegetable crops through altering the PA catabolism are enumerated. Finally, several other vital questions that remain unanswered are proposed and discussed. These include the mechanisms underlying the cooperative regulation of developmental processes by PAs and their interplaying partners like phytohormones, H2O2 and NO; PA transport for maintaining homeostasis; and utilization of PA anabolism/catabolism for generating high-yield and good-quality crops. This review aims to gain new insights into the pleiotropic role of PAs in the modulation of plant growth and development, which provides an alternative approach for manipulating and engineering valuable crop varieties that can be used in the future.

Overexpression of OsACL5 triggers environmentally-dependent leaf rolling and reduces grain size in rice.

Major polyamines include putrescine, spermidine, spermine and thermospermine, which play vital roles in growth and adaptation against environmental changes in plants. Thermospermine (T-Spm) is synthetised by ACL5. The function of ACL5 in rice is still unknown. In this study, we used a reverse genetic strategy to investigate the biological function of OsACL5. We generated several knockout mutants by pYLCRISPR/Cas9 system and overexpressing (OE) lines of OsACL5. Interestingly, the OE plants exhibited environmentally-dependent leaf rolling, smaller grains, lighter 1000-grain weight and reduction in yield per plot. The area of metaxylem vessels of roots and leaves of OE plants were significantly smaller than those of WT, which possibly caused reduction in leaf water potential, resulting in leaf rolling with rise in the environmental temperature and light intensity and decrease in humidity. Additionally, the T-Spm contents were markedly increased by over ninefold whereas the ethylene evolution was reduced in OE plants, suggesting that T-Spm signalling pathway interacts with ethylene pathway to regulate multiple agronomic characters. Moreover, the osacl5 exhibited an increase in grain length, 1000-grain weight, and yield per plot. OsACL5 may affect grain size via mediating the expression of OsDEP1, OsGS3 and OsGW2. Furthermore, haplotypes analysis indicated that OsACL5 plays a conserved function on regulating T-Spm levels during the domestication of rice. Our data demonstrated that identification of OsACL5 provides a theoretical basis for understanding the physiological mechanism of T-Spm which may play roles in triggering environmentally dependent leaf rolling; OsACL5 will be an important gene resource for molecular breeding for higher yield.

High purity of human secreted phospholipase A2 group IIE in Pichia pastoris using basal salts medium comparison with YPD medium.

Secreted phospholipase A2s (sPLA2s) are a group of enzymes with 6-8 disulfide bonds that participate in numerous physiological processes by catalyzing the hydrolysis of phospholipids at the sn-2 position. Due to their high content of disulfide bonds and hydrolytic activity toward cell membranes, obtaining the protein of sPLA2s in the soluble and active form is challenging, which hampers their functional study. In this study, one member of recombinant human sPLA2s, tag-free group IIE (GIIE), was expressed in Pichia pastoris. The protein GIIE was purified from the crude culture supernatant by a two-step chromatography procedure, a combination of cation exchange and size-exclusion chromatography. In the shake flask fermentation, Protein of GIIE with higher purity was successfully obtained, using basal salts medium (BSM) instead of YPD medium. In the large-scale fermentation, each liter of BSM produced a final yield of 1.2 mg pure protein GIIE. This protocol will facilitate further research of GIIE and provide references for the production of other sPLA2 members.

Effects of polyvinylchloride microplastics on the toxicity of nanoparticles and antibiotics to aerobic granular sludge: Nitrogen removal, microbial community and resistance genes.

Copper oxide nanoparticles (CuO NPs) and ciprofloxacin (CIP) have ecological risk to humans and ecosystems. Polyvinylchloride microplastics (PVC MPs), as a representative of microplastics, may often coexist with CuO NPs and CIP in wastewater treatment systems due to their widespread application. However, the co-impact of PVC MPs in wastewater systems contained with CuO NPs and CIP on nitrogen removal and ecological risk is not clear. In this work, PVC MPs co-impacts on the toxicity of CuO NPs and CIP to aerobic granular sludge (AGS) systems and potential mechanisms were investigated. 10 mg/L PVC MPs co-addition did not significantly affect the nitrogen removal, but it definitely changed the microbial community structure and enhanced the propagation and horizontal transfer of antibiotics resistance genes (ARGs). 100 mg/L PVC MPs co-addition resulted in a raise of CuO NP toxicity to the AGS system, but reduced the co-toxicity of CuO NPs and CIP and ARGs expression. The co-impacts with different PVC MPs concentration influenced Cu2+ concentrations, cell membrane integrity, extracellular polymeric substances (EPS) contents and microbial communities in AGS systems, and lead to a change of nitrogen removal.

A liquid chromatography-tandem mass spectrometry method for comprehensive determination of metabolites in the purine pathway of rat plasma and its application in anti-gout effects of Lycium ruthenicum Murr.

It has been proved that purine metabolites are implicated in various biological syndromes and disorders. Therefore, the realization of panoramic detection of purine metabolites will be of great significance to the pathogenesis of purine metabolic disorders. In the present study, an ultra-high performance liquid chromatography with tandem mass spectrometry method was developed for the comprehensive quantification of purine metabolites in rat plasma. The 17 purine metabolites were separated and quantified in the short running time of 15 min. The proposed method was strictly validated by applying SeraSub solution as a matrix and proved to be linear (R2 ≥ 0.9944), accurate (the recoveries of all analytes ranged from 85.3% to 103.0%, with relative standard deviation values ≤ 9.3%), and precise (the intra- and inter-day precisions were less than 10.8% and 12.4%, respectively). The method was then successfully applied to the qualification of the endogenous purine metabolites in acute gouty arthritis rats, as well as colchicine and anthocyanin-intervened rats. Results showed that uric acid, xanthine, hypoxanthine, and xanthine were considered the key factors of acute gouty arthritis. The established method and measurement of purines in rat plasma might help the investigation of the action mechanisms between purine disorders and related diseases.

Sumoylation of SMAD 4 ameliorates the oxidative stress-induced apoptosis in osteoblasts.

Oxidative stress-induced mitochondrial function and cell apoptosis to osteoblasts, plays a critical role in the pathophysiology of osteoporosis. However, mechanisms underlying such process remain not yet clear. We aims in this study to investigate a possible role of SMAD (the mothers against decapentaplegic homolog 4 (SMAD4) in the oxidative stress-induced apoptosis, in homo sapiens osteoblast hFOB1.19 cells. Results demonstrated that the treatment with more than 100µM H2O2 significantly downregulated the cellular viability, whereas markedly induced apoptosis in hFOB1.19 cells. The SMAD4 was markedly reduced in both mRNA and protein levels in the H2O2 -treated hFOB1.19 cells, along with the reduction of Small ubiquitin-related modifier 1 (SUMO 1) and SUMO 2/3. The immunoprecipitation assay confirmed indicated the interaction between SUMO 1 (or SUMO 2/3) and SMAD4. Moreover, the SMAD4 overexpression markedly ameliorated the H2O2-resulted viability reduction and apoptosis induction in hFOB1.19 cells. Interestingly, such amelioration was blocked by the knockdown of SUMO 2/3. Taken together, we conclued that SMAD4 inhibits the H2O2-induced apoptosis in osteoblast hFOB1.19 cells; such inhibition might depend on the SUMOylation by SUMO 2/3. It implies a promising role of SMAD4 in oxidative stress-promoted damage to osteoblasts.

[Concentration of red blood cell folate and the analysis of folic acid supplement optimum time and dose in first trimester].

OBJECTIVE: To have a knowledge of prevalent red blood cell folate concentration in Beijing and analyzes optimum time and dose of folic acid supplement. To provide the basis data for making public health policy and clinical consultation. METHODS: This study included 3458 pregnant women who visited nutrition outpatient of the Haidian Maternal and Child Health Hospital in Beijing in first trimester. Their last menstrual period is between 1st Feb 2014 and 31 st Jan 2016. Using the method of cross sectional study to collect their demographic information, folic acid supplementation, clinical information and venous blood samples. Competitive binding receptor assay was used for detecting the red blood cell folate concentration. RESULTS: The mean of red blood cell folate concentration was( 806. 5 ± 273. 7) ng/mL. The red blood cell folate concentration differences between age groups were significant( P < 0. 001). Women with graduate and above had higher red blood cell folate concentration than others( P = 0. 030). Women whose family income > 10000 had higher red blood cell folate concentration than other groups( P < 0. 001). Red blood cell folate concentration in summer and autumn higherthan other season( P < 0. 001). Red blood cell folate concentration level increased with folic acid supplementation dose and time. 84. 3% the pregnant women reached 1180nmol/L( 521 ng/mL) and 90. 0% could reach the reference if used 400 µg folic acid supplemented for 16 weeks or ≥600 µg more than 8 weeks. CONCLUSION: Age, education level and family income are associated with red blood cell folate concentration. Depending on red blood cell folate concentration to advise the time and dose of folic acid supplementation.

Multifunctional BSA-Au nanostars for photoacoustic imaging and X-ray computed tomography.

We report the synthesis and characterization of bovine serum albumin-capped Au nanostars (BSA-AuNSs) for dual-modal computed tomography (CT)/photoacoustic (PA) imaging application. The BSA-AuNSs have an average size of 85nm, and a surface plasmon resonance (SPR) peak at approximately 770nm. They have excellent biocompatibility, good X-ray attenuation, and great PA contrast enhancement properties. When injected intravenously, liver signal markedly increases in both CT and PA modalities. The in vivo biodistribution studies and pathology results showed that the BSA-AuNSs were mainly excreted through the liver and intestines with no obvious biotoxicity. These results indicate that BSA-AuNSs have high potential to be used as dual-modal CT/PA imaging contrast agents or further used to develop targeted probes. This preliminary study suggests that PA tomography may be used to non-invasively trace the kinetics and biodistribution of the nanoparticles.

A case-control study of high-intensity focused ultrasound combined with sonographically guided intratumoral ethanol injection in the treatment of uterine fibroids.

OBJECTIVES: The purpose of this study was to explore the feasibility of high-intensity focused ultrasound combined with sonographically guided intratumoral ethanol injection in the treatment of uterine fibroids and to compare its therapeutic effects and potential side effects with those of simple high-intensity focused ultrasound treatment. METHODS: Forty patients with uterine fibroids from the Department of Ultrasonography in our hospital were randomly divided into 2 groups of the same size: group H, which only underwent high-intensity focused ultrasound treatment; and group H + A, which underwent sonographically guided intratumoral ethanol injection therapy first and then high-intensity focused ultrasound treatment the following day. The treatment times, treatment doses, pain scores, side effects, and therapeutic effect rates of the groups were then recorded and compared. RESULTS: Both the treatment time and dose of group H + A were significantly less than those of group H, and the differences were statistically significant (P < .05). A lower pain score and fewer side effects were achieved in group H + A, also with statistically significant differences (P < .05). The therapeutic effect rate of group H + A was also higher than that of group H, and the difference was also statistically significant (P < .05). CONCLUSIONS: In the treatment of uterine fibroids, high-intensity focused ultrasound combined with sonographically guided intratumoral ethanol injection requires less treatment time and a lower dose than simple high-intensity focused ultrasound treatment and significantly reduces the pain and side effects commonly experienced by patients. High-intensity focused ultrasound combined with sonographically guided intratumoral ethanol injection is a feasible, safe, and more effective way to treat patients with uterine fibroids.

Maternal fasting serum C-peptide concentrations in the first and second trimesters and subsequent risk of gestational diabetes mellitus: A nested case-control study among Chinese women.

OBJECTIVE: To examine the association of serum connecting peptide (C-peptide) concentrations with gestational diabetes mellitus (GDM) risk among Chinese women. METHODS: A nested case-control study was conducted on 436 reproductive-aged women, involving 218 GDM cases and 218 controls matched at 1:1 by maternal age, in Beijing, China between January 2016 and December 2017. Fasting serum C-peptide were successively determined at 10-14 and 15-20 weeks of gestation. Restricted cubic spline and logistic regression analyses were utilized, and receiver operating characteristic (ROC) curves were generated to evaluate the predictive capacity of C-peptide for GDM. RESULTS: Fasting serum C-peptide concentrations exhibited a significant decrease from the initial to the subsequent trimester in females with normal glucose tolerance (NGT). For each 1 log ng/mL increase of fasting serum C-peptide during the first and second trimesters, GDM risk increased by 2.38-fold [odds ratio (OR): 2.38, 95% confidence intervals (95%CI): 1.33-4.40] and 3.07-fold (OR: 3.07, 95%CI: 1.49-6.62), respectively. The areas under the ROC curves for the first- and second-trimester C-peptide were 80.4% and 82.4%. CONCLUSION: Our findings revealed a positive correlation between fasting serum C-peptide during the first and second trimesters and the risk of GDM or its subtypes, underscoring the potential of C-peptide as a predictor for GDM development.

Co-existence effect of copper oxide nanoparticles and ciprofloxacin on simultaneous nitrification, endogenous denitrification, and phosphorus removal by aerobic granular sludge.

Nanoparticles and antibiotics are toxic to humans and ecosystems, and they inevitably coexist in the wastewater treatment plants. Hence, the co-existence effects and stress mechanism of copper (II) oxide nanoparticles (CuO NPs) and ciprofloxacin (CIP) on simultaneous nitrification, endogenous denitrification and phosphorus removal (SNEDPR) by aerobic granular sludge (AGS) were investigated here. The co-existence stress of 5 mg/L CuO NPs and 5 mg/L CIP resulted in the synergistic inhibitory effect on nutrient removal. Transformation inhibition mechanisms of carbon (C), nitrogen (N) and phosphorus (P) with CuO NPs and CIP addition were time-dependent. Furthermore, the long-term stress mainly inhibited PO43--P removal by inhibiting phosphorus release process, while short-term stress mainly inhibited phosphorus uptake process. The synergistic inhibitory effect of CuO NPs and CIP may be due to the changes of physicochemical characteristics under the co-existence of CuO NPs and CIP. This further altered the sludge characteristics, microbial community structure and functional metabolic pathways under the long-term stress. Resistance genes analysis exhibited that the co-existence stress of CuO NPs and CIP induced the amplification of qnrA (2.38 folds), qnrB (4.70 folds) and intI1 (3.41 folds) compared with the control group.

Rapid start-up of partial nitrification reactor by exogenous AHLs and Vanillin combined with intermittent aeration.

Quorum sensing (QS) and quorum quenching (QQ) are common phenomena in microbial systems and play an important role in the nitrification process. However, rapidly start up partial nitrification regulated by N-acyl-homoserine lactones (AHLs)-mediated QS or QQ has not been reported. Hence, we chose N-butyryl homoserine lactone (C4-HSL) and N-hexanoyl homoserine lactone (C6-HSL) as the representative AHLs, and Vanillin as the representative quorum sensing inhibitor (QSI) combined intermittent aeration to investigate their effects on the start-up process of partial nitrification. The start-up speed in the group with C4-HSL or C6-HSL addition was 1.42 or 1.26 times faster than that without addition, respectively. Meanwhile, the ammonium removal efficiency with C4-HSL or C6-HSL addition was increased by 13.87 % and 17.30 % than that of the control group, respectively. And, partial nitrification could maintain for a certain period without AHLs further addition. The increase of Nitrosomonas abundance and ammonia monooxygenase (AMO) activity, and the decrease of Nitrobacter abundance and nitrite oxidoreductase (NXR) activity were the reasons for the rapid start-up of partial nitrification in the AHLs groups. Vanillin addition reduced AMO and hydroxylamine oxidoreductase (HAO) activity, and increased Nitrobacter abundance and NXR activity, thus these were not conducive to achieving partial nitrification. Denitrifying bacteria (Hydrogenophaga, Thauera and Aquimonas) abundance increased in the Vanillin group. QS-related bacteria and gene abundance were elevated in the AHLs group, and reduced in the Vanillin group. Function prediction demonstrated that AHLs promoted the nitrogen cycle while Vanillin enhanced the carbon cycle. This exploration might provide a new technical insight into the rapid start-up of partial nitrification based on QS control.

Hematological Parameters in the First Trimester and the Risk of Gestational Diabetes Mellitus - Beijing, China, 2017-2020.

What is already known about this topic?: Hematological parameters may indicate the presence of chronic low-grade inflammation and increasing viscosity, which are involved in the pathological processes of gestational diabetes mellitus (GDM). However, the association between several hematological parameters in early pregnancy and GDM has yet to be elucidated. What is added by this report?: Hematological parameters in the first trimester, particularly red blood cell (RBC) count and systematic immune index, have a significant impact on GDM incidence. The neutrophils (NEU) count in the first trimester was particularly pronounced for GDM. The upward trend of RBC, white blood cell (WBC), and NEU counts was consistent across all GDM subtypes. What are the implications for public health practice?: Early pregnancy hematological parameters are associated with the risk of GDM.

Novel albendazole-glucan particles for enhancing intestinal absorption and improving hepatic targeting.

Background: Glucan particles (GPs) are derived from the Saccharomyces cerevisiae cell wall. The hollow particles composed of ß-1,3-D-glucan have been extensively studied in terms of immune regulation and macrophage-targeted drug delivery. Albendazole (ABZ) is a benzimidazole drug with good anti-parasitic activity and is the drug recommended by the World Health Organization for the first-line treatment of hydatid disease. Methods: A dynamic light scatterometer, scanning electron microscope, and transmission electron microscope were used to characterize the ABZ-GPs. High-performance liquid chromatography (HPLC), laser scanning confocal microscope (LSCM) and an in vivo small animal imaging system were used to evaluate theability of ABZ-GPs to be recognized by macrophages, whether ABZ-GPs are more readily absorbed and eliminated in the blood than the original ABZ drug in rats, and the ability of ABZ-GPs to target the mouse liver. Results: The ABZ-GPs were successfully constructed to achieve fluorescence, magnetic resonance imagining, and laser confocal microscopy imaging. The glucan shell effectively protects ABZ from enzymatic degradation and from being pumped out in the gastrointestinal tract. The analysis of ABZ and its major metabolite albendazole sulfoxide in the rat plasma and mouse liver showed that compared to the ABZ suspension group, the degradation of ABZ-GPSs in the blood was low, and the targeting of ABZ-GPSs in the liver was significantly enhanced. Conclusions: In the oral treatment of hepatic hydatid disease, GPs can be used as carriers to achieve the targeted transport of ABZ, which in turn can be used for the targeted therapy of liver echinococcosis. Thus, ABZ-GPs may be a promising form of targeted therapy.

Maternal exposure to traffic-related ambient particles and risk of gestational diabetes mellitus with isolated fasting hyperglycaemia: A retrospective cohort study in Beijing, China.

BACKGROUND: Ambient particles have been associated with gestational diabetes mellitus (GDM), however, no study has evaluated the effects of traffic-related ambient particles on the risks of GDM subgroups classified by oral glucose tolerance test (OGTT) values. METHODS: A retrospective analysis was conducted among 24,001 pregnant women who underwent regular prenatal care and received OGTT at Haidian Maternal and Child Health Hospital in Beijing, China, 2014-2017. A total of 3,168 (13.2%) pregnant women were diagnosed with GDM, including 1,206 with isolated fasting hyperglycaemia (GDM-IFH). At a fixed-location monitoring station, routinely monitored ambient particles included fine particulate matter (PM2.5), black carbon (BC) and particles in size ranges of 5-560 nm (PNC5-560). Contributions of PNC5-560 sources were apportioned by positive matrix factorization model. Logistic regression model was applied to estimate odds ratio (OR) of ambient particles on GDM risk. RESULTS: Among the 24,001 pregnancy women recruited in this study, 3,168 (13.2%) were diagnosed with GDM, including 1,206 with isolated fasting hyperglycaemia (GDM-IFH) and 1,295 with isolated post-load hyperglycaemia (GDM-IPH). We observed increased GDM-IFH risk with per interquartile range increase in first-trimester exposures to PM2.5 (OR = 1.94; 95% Confidence Intervals: 1.23-3.07), BC (OR = 2.14; 1.73-2.66) and PNC5-560 (OR = 2.46; 1.90-3.19). PNC5-560 originated from diesel and gasoline vehicle emissions were found in associations with increases in GDM-IFH risk, but not in GDM-IPH risk. CONCLUSION: Our findings suggest that exposure to traffic-related ambient particles may increase GDM risk by exerting adverse effects on fasting glucose levels during pregnancy, and support continuing efforts to reduce traffic emissions for protecting vulnerable population who are at greater risk of glucose metabolism disorder.

Maternal exposures to fine and ultrafine particles and the risk of preterm birth from a retrospective study in Beijing, China.

Maternal exposure to fine particulate matter (PM2.5) has been associated with increased risk of preterm birth (PTB), but evidence on particles in smaller sizes and PTB risk remains limited. In this retrospective analysis, we included birth records of 24,001 singleton live births from Haidian Maternal and Child Health Hospital in Beijing, China, 2014-2017. Concurrently, number concentrations of size-fractioned particles in size ranges of 5-560 nm (PNC5-560) and mass concentrations of PM2.5, black carbon (BC) and gaseous pollutants were measured from a fixed-location monitoring station in central Haidian District. Logistic regression models were used to estimate the odds ratio (OR) of air pollutants on PTB risk after controlling for temperature, relative humidity, and individual covariates (e.g., maternal age, ethnicity, gravidity, parity, gestational weight gain, fetal gender, the year and season of conception). Positive matrix factorization models were then used to apportion the sources of PNC5-560. Among the 1062 (4.4%) PTBs, increased PTB risk was observed during the third trimester of pregnancy per 10 µg/m3 increase in PM2.5 [OR = 1.92; 95% Confidence Interval (95% CI): 1.76, 2.09], per 1000 particles/cm3 increase in PNC25-100 (OR = 1.09; 95% CI: 1.03, 1.15) and PNC100-560 (OR = 1.22; 95% CI: 1.05, 1.42). Among the identified sources of PNC5-560, emissions from gasoline and diesel vehicles were significantly associated with increased PTB risk, with ORs of 1.14 (95% CI: 1.01, 1.29) and 1.11 (95% CI: 1.04, 1.18), respectively. Exposures to other traffic-related air pollutants, such as BC and nitrogen dioxide (NO2) were also significantly associated with increased PTB risk. Our findings highlight the importance of traffic emission reduction in urban areas.

Trends in 340B Drug Pricing Program Contract Growth Among Retail Pharmacies From 2009 to 2022.

This cross-sectional study assesses the increases and decreases over time in the number of pharmacy contracts, distance from contracting pharmacies, and proportion of pharmacy contracts with safety-net practices in the US.

Changes in the levels of CD4+ and CD8+ T-lymphocytes after strontium-89 chloride therapy for painful bone metastases in patients correlate with treatment efficacy.

The aim of this study was to evaluate changes in the peripheral blood CD(4)(+) and CD(8)(+) T-lymphocyte populations following strontium-89 chloride ((89)SrCl(2)) therapy for painful bone metastases and to relate these changes to a therapeutic response. Forty-two (42) patients with painful bone metastases were treated with 148 MBq (4 mCi) of (89)SrCl(2). Blood samples were drawn before and monthly for 6 months after the treatment. CD(4)(+) and CD(8)(+) T-lymphocyte levels were measured using flow cytometry. The number of bone metastases and the pain score were used to assess the effect of therapy. Before the administration of (89)SrCl(2), the ratio of CD(4)(+) to CD(8)(+) T-lymphocytes was lower in patients with bone metastases than in the control subjects (p < 0.01); after therapy, the ratio increased up to the fourth month and then gradually declined to pretreatment levels. Responders had higher post-therapeutic ratios of CD(4)(+) to CD(8)(+) than nonresponders. There was a good correlation between the ratio of CD(4)(+) to CD(8)(+) and both the number of bone metastases and the pain score. The ratio of CD(4)(+) to CD(8)(+) T-lymphocytes correlated strongly with the response of bone metastases to (89)SrCl(2), and therefore, may be used as an indicator of (89)SrCl(2) efficacy.

Serum concentrations of IL-2 and TNF-alpha in patients with painful bone metastases: correlation with responses to 89SrCl2 therapy.

UNLABELLED: We have used 89SrCl2 for the palliative treatment of painful bone metastases from various malignant diseases. We studied the correlation between serum interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) levels and the response to 89SrCl2 therapy. METHODS: Forty-two patients (24 men and 18 women) were treated intravenously with 89SrCl2 at a dose of 148 MBq (4 mCi). RESULTS: The response rate was 33 of 42 (79%). In the control subjects, serum IL-2 concentrations were higher but TNF-alpha concentrations lower (P < 0.05) than in the patients with bone metastases. After treatment with 89SrCl2, IL-2 levels increased and TNF-alpha levels decreased, with maximal changes at the fourth month after therapy. After comparing the serum levels of IL-2 and TNF-alpha between responders and nonresponders, we found that these variables did not differ before 89SrCl2 therapy but differed significantly (P < 0.05) after therapy. Responders had higher IL-2 and lower TNF-alpha concentrations than nonresponders. A good correlation was found between IL-2 and TNF-alpha levels and the number of metastases and pain score. CONCLUSION: 89SrCl2 is effective for palliation of bone pain in patients with disseminated bone metastases. In addition to managing pain, 89SrCl2 can improve immunity and the quality of life for most patients. Further studies are needed to elucidate the roles of IL-2 and TNF-alpha in the response to 89SrCl2 therapy and to evaluate their usefulness as indicators of 89SrCl2 efficacy.

Annexin A2 Coordinates STAT3 to Regulate the Invasion and Migration of Colorectal Cancer Cells In Vitro.

The present study aimed to reveal the expression of STAT3 and Anxa 2 in CRC specimens and to investigate the effects of STAT3 and Anxa 2 signaling on the proliferation, invasion, and migration in CRC Caco-2 cells. Results demonstrated that both Anxa 2 and STAT3 were highly expressed in CRC specimens in both mRNA and protein levels, with or without phosphorylation (Tyrosine 23 in Anxa 2 and Tyrosine 705 in STAT3). And the upregulated Anxa 2 promoted the phosphorylation of STAT3 (Tyrosine 705) in CRC Caco-2 cells. The upregulated Anxa 2 promoted the proliferation, migration, and invasion of Caco-2 cells in vitro. Moreover, the STAT3 knockdown also repressed the proliferation, migration, and invasion of Caco-2 cells. In conclusion, the overexpressed Annexin A2 regulated the proliferation, invasion, and migration in CRC cells in an association with STAT3.